title: Life spanning murine gene expression profiles in relation to chronological and pathological aging in multiple organs.
abstract: Aging and age-related pathology is a result of a still incompletely understood intricate web of molecular and cellular processes. We present a C57BL/6J female mice in vivo aging study of five organs (liver, kidney, spleen, lung, and brain), in which we compare genome-wide gene expression profiles during chronological aging with pathological changes throughout the entire murine life span (13, 26, 52, 78, 104, and 130 weeks). Relating gene expression changes to chronological aging revealed many differentially expressed genes (DEGs), and altered gene sets (AGSs) were found in most organs, indicative of intraorgan generic aging processes. However, only ≤ 1% of these DEGs are found in all organs. For each organ, at least one of 18 tested pathological parameters showed a good age-predictive value, albeit with much inter- and intraindividual (organ) variation. Relating gene expression changes to pathology-related aging revealed correlated genes and gene sets, which made it possible to characterize the difference between biological and chronological aging. In liver, kidney, and brain, a limited number of overlapping pathology-related AGSs were found. Immune responses appeared to be common, yet the changes were specific in most organs. Furthermore, changes were observed in energy homeostasis, reactive oxygen species, cell cycle, cell motility, and DNA damage. Comparison of chronological and pathology-related AGSs revealed substantial overlap and interesting differences. For example, the presence of immune processes in liver pathology-related AGSs that were not detected in chronological aging. The many cellular processes that are only found employing aging-related pathology could provide important new insights into the progress of aging.
authors.affiliation: University of Amsterdam (UvA), MicroArray Department & Integrative Bioinformatics Unit (MAD-IBU), Swammerdam Institute for Life Sciences (SILS), Faculty of Science (FNWI), Amsterdam, the Netherlands.|Netherlands Bioinformatics Centre (NBIC), Nijmegen, the Netherlands.
authors.forename: Martijs J
authors.initials: MJ
authors.lastname: Jonker
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Center for Health Protection, Bilthoven, the Netherlands.|Leiden University Medical Center, Department of Toxicogenetics, Leiden, the Netherlands.
authors.forename: Joost Pm
authors.initials: JP
authors.lastname: Melis
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Center for Health Protection, Bilthoven, the Netherlands.|Dutch Molecular Pathology Center, Department of Pathobiology, Faculty of veterinary medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Raoul V
authors.initials: RV
authors.lastname: Kuiper
authors.affiliation: University of Amsterdam (UvA), MicroArray Department & Integrative Bioinformatics Unit (MAD-IBU), Swammerdam Institute for Life Sciences (SILS), Faculty of Science (FNWI), Amsterdam, the Netherlands.
authors.forename: Tessa V
authors.initials: TV
authors.lastname: van der Hoeven
authors.affiliation: University of Amsterdam (UvA), MicroArray Department & Integrative Bioinformatics Unit (MAD-IBU), Swammerdam Institute for Life Sciences (SILS), Faculty of Science (FNWI), Amsterdam, the Netherlands.|Netherlands Bioinformatics Centre (NBIC), Nijmegen, the Netherlands.|National Institute for Public Health and the Environment (RIVM), Center for Health Protection, Bilthoven, the Netherlands.
authors.forename: P F K
authors.initials: PFK
authors.lastname: Wackers
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Center for Health Protection, Bilthoven, the Netherlands.|Dutch Molecular Pathology Center, Department of Pathobiology, Faculty of veterinary medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Joke
authors.initials: J
authors.lastname: Robinson
authors.affiliation: Erasmus University Medical Center, CGC Department of Genetics, Rotterdam, The Netherlands.
authors.forename: Gijsbertus Tj
authors.initials: GT
authors.lastname: van der Horst
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Center for Health Protection, Bilthoven, the Netherlands.
authors.forename: Martijn Et
authors.initials: ME
authors.lastname: Dollé
authors.affiliation: Albert Einstein College of Medicine, Department of Genetics, New York, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Vijg
authors.affiliation: University of Amsterdam (UvA), MicroArray Department & Integrative Bioinformatics Unit (MAD-IBU), Swammerdam Institute for Life Sciences (SILS), Faculty of Science (FNWI), Amsterdam, the Netherlands.|Netherlands Bioinformatics Centre (NBIC), Nijmegen, the Netherlands.
authors.forename: Timo M
authors.initials: TM
authors.lastname: Breit
authors.affiliation: Erasmus University Medical Center, CGC Department of Genetics, Rotterdam, The Netherlands.
authors.forename: Jan Hj
authors.initials: JH
authors.lastname: Hoeijmakers
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Center for Health Protection, Bilthoven, the Netherlands.|Leiden University Medical Center, Department of Toxicogenetics, Leiden, the Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: van Steeg
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D007668:Kidney / Q000502:physiology; D008099:Liver / Q000502:physiology; D008168:Lung / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000502:physiology; D016019:Survival Analysis
keywords: aging dynamics; database; gene expression; in vivo; pathology